PREreview structurée de Relevance of Seasonal Revaccination against Respiratory Syncytial Virus in Hematology Patients: First Insights in Stem Cell Transplant Recipients

Does the introduction explain the objective of the research presented in the preprint?

Yes

Yes. The authors clearly explain the research objectives and provide relevant background on the current condition of vaccination against RSV among HSCT patients. The authors then discuss two important questions that the duration of vaccine protection remains poorly documented in seroresponders, and the probability of revaccination to improve immunogenicity in non-seroresponding patients remains unclear. To address above problems, the authors followed antibody responses over 12 months in 71 HSCT recipients and explored the potential benefits of revaccination before the next RSV season.

Are the methods well-suited for this research?

Somewhat appropriate

The methods are somewhat well-suited for this research because the objectives are to evaluate the duration of antibody responses after RSV vaccination and the benefits of seasonal revaccination in HSCT recipients. The longitudinal observational study design is a good choice because it allows authors to follow changes in antibody responses over 12 months. The study had 71 adult recipients of allogeneic HSCT who received a single dose of the bivalent RSVpreF vaccine and divided them into early-vaccinated(≤18 months) and late-vaccinated(>18 months) groups. 13 patients of the early-vaccinated and 9 from the late-vaccinated group were revaccinated one year later. The authors used the ELISA assay to measure anti-RSVpreF IgG levels. I think this lab-confirmed measurement is a strength because it provides more reliable data and result on immune responses comparing with self-reported method. The authors used the Mann-Whitney test to compare continuous variables and PCR-confirmed RSV infections before and after vaccine introduction. However, the study has several limitations. First, the revaccination subgroup was small with only 22 patients. And authors didn't clearly explain how these 22 patients were selected from 71 recipients for revaccination. I think this may introduce potential selection bias and affect the generalizability of findings. The authors acknowledge that the small sample size prevented multivariable analyses. Second, the early and late vaccination groups differed in many other clinical characteristics, such as immunosuppressive treatment and lymphocyte counts. These differences may also influence antibody responses except vaccination timing. Third, the statistical methods for analyzing repeated antibody measurements were not clearly explained, although the authors reported using the Mann-Whitney test. To improve: The authors could provide more information about how 22 patients were selected for revaccination from 71 recipients. The authors should also discuss how differences in other clinical characteristics like immune status and immunosuppressive treatment between the early and late vaccination groups might affect the observed antibody responses. It would be better to clarify which statistical methods were used to analyze repeated antibody measurements and whether correlations within the same patients were considered.

Are the conclusions supported by the data?

Somewhat supported

The conclusions are reasonable and not overreaching interpretations of the data. The authors provide evidence that revaccination may improve antibody responses in HSCT recipients, especially early-vaccinated patients after transplantation. For example, the early-vaccinated group had a lower seroconversion rate compared with the late-vaccinated group (14% vs. 63%). After revaccination, the early group showed a 23-fold increase in antibody levels, compared with a 4-fold increase in the late group. The authors also found that both groups achieved comparable antibody titers after revaccination. However, I think some conclusions may be stronger beyond the data. First, the revaccination subgroup had only 22 patients, and the difference in antibody fold changes between the two groups was not statistically significant. The authors acknowledge some limitations, including the small sample size and the lack of multivariable analyses, but the recommendation for systematic revaccination may still be unsure. The authors could also more clearly distinguish between improved antibody responses and clinical effectiveness. For example, they stated that revaccination is beneficial for patients who initially responded poorly, but the study mainly measured antibody responses instead of clinical protection.

Are the data presentations, including visualizations, well-suited to represent the data?

Somewhat appropriate and clear

The data presentations are appropriate and clear. Figure 1 shows the changes in antibody responses over time and after revaccination, and Table 1 shows the characteristics of patients in the early-vaccinated and late-vaccinated groups. I think the different colors and individual data points in Figure 1 are helpful to understand the differences between groups. However, I think Table 1 has too much information, and I would recommend improving the format and organization. It would be helpful to identify differences between the two groups.

How clearly do the authors discuss, explain, and interpret their findings and potential next steps for the research?

Somewhat clearly

The authors explain that initial nonresponders may benefit from revaccination. They also discuss that the improved antibody responses may be related to immune recovery over time after HSCT. However, I think the authors could further explain how immune recovery and immunosuppressive treatment might affect the observed responses to revaccination. Then, the limitations of the study are effectively addressed, including the small sample size, lack of multivariable analyses, and evaluation of only one RSV vaccine. Finally, the authors suggest that future studies should figure out potential usefulness of revaccination in late-vaccinated patients, systematic revaccination strategies, and individual differences in immune recovery. They also encourage future research in other immunocompromised populations.

Is the preprint likely to advance academic knowledge?

Somewhat likely

The preprint makes several meaningful contributions to RSV vaccination in HSCT recipients, especially for the duration of antibody responses and the potential benefits of seasonal revaccination. Previous studies mainly focused on the initial immune responses after RSV vaccination, but this preprint provides more information about long-term antibody responses and revaccination. However, this preprint has a small sample size, which limits the strength and generalizability of the findings. Also, the preprint mainly evaluated antibody responses rather than clinical protection against RSV infection. Therefore, the results are not sufficient to confirm the benefits of seasonal revaccination.

Would it benefit from language editing?

No

Would you recommend this preprint to others?

Yes, but it needs to be improved

After acknowledging some of the limitations of the study, this preprint could be helpful for clinicians and researchers who are interested in RSV vaccination strategies for HSCT recipients. Also, those studying vaccine immunogenicity and seasonal revaccination in immunocompromised patients may find the findings useful. However, further research with larger sample sizes and clinical outcomes is needed.

Is it ready for attention from an editor, publisher or broader audience?

Yes, after minor changes

I would recommend further explanation of the patient selection for revaccination and the statistical methods used for repeated antibody measurements before wider dissemination.

Competing interests

The author declares that they have no competing interests.

Use of Artificial Intelligence (AI)

The author declares that they did not use generative AI to come up with new ideas for their review.